U.S. patent application number 13/383161 was filed with the patent office on 2012-05-10 for composite bone cements with a pmma matrix, containing bioactive antibacterial glasses or glassceramics.
This patent application is currently assigned to UNIVERSITA' DEGLI STUDI DI TORINO. Invention is credited to Alessandro Bistolfi, Maurizio Crova, Sara Ferraris, Giovanni Maina, Alessandro Masse, Marta Miola, Enrica Verne'.
Application Number | 20120115981 13/383161 |
Document ID | / |
Family ID | 41718214 |
Filed Date | 2012-05-10 |
United States Patent
Application |
20120115981 |
Kind Code |
A1 |
Verne'; Enrica ; et
al. |
May 10, 2012 |
COMPOSITE BONE CEMENTS WITH A PMMA MATRIX, CONTAINING BIOACTIVE
ANTIBACTERIAL GLASSES OR GLASSCERAMICS
Abstract
A bone cement comprising an acrylic polymeric component and an
inorganic component comprising a bioactive glass or glass-ceramic,
comprising at least one metal oxide having an anti-bacterial
activity, wherein said glass or glass-ceramic component is adapted
to release ions of said metal in contact with physiological fluids.
The bone cement performs a sustained antibacterial action, also
promoting binding with the tissues with which it is contacted, and
it is advantageously employed in the fixation of orthopaedic
prostheses, in the production of temporary prostheses and in spinal
surgery.
Inventors: |
Verne'; Enrica; (Torino,
IT) ; Miola; Marta; (La Cassa (Torino), IT) ;
Ferraris; Sara; (Grugliasco (Torino), IT) ; Masse;
Alessandro; (Torino, IT) ; Bistolfi; Alessandro;
(Torino, IT) ; Crova; Maurizio; (Pecetto Torinese
(Torino), IT) ; Maina; Giovanni; (Baldissero Torinese
(Torino), IT) |
Assignee: |
UNIVERSITA' DEGLI STUDI DI
TORINO
Torino
IT
POLITECNICO DI TORINO
Torino
IT
|
Family ID: |
41718214 |
Appl. No.: |
13/383161 |
Filed: |
July 12, 2010 |
PCT Filed: |
July 12, 2010 |
PCT NO: |
PCT/IB10/53181 |
371 Date: |
January 9, 2012 |
Current U.S.
Class: |
523/117 ;
523/116 |
Current CPC
Class: |
A61L 24/0089 20130101;
A61L 2430/02 20130101; A61L 24/0015 20130101; A61L 24/0089
20130101; A61L 2300/102 20130101; C08L 33/12 20130101 |
Class at
Publication: |
523/117 ;
523/116 |
International
Class: |
C08K 3/40 20060101
C08K003/40; C08L 33/10 20060101 C08L033/10 |
Foreign Application Data
Date |
Code |
Application Number |
Jul 10, 2009 |
IT |
TO2009A000518 |
Claims
1-16. (canceled)
17. A bone cement comprising an acrylic polymeric component and an
inorganic component comprising a bioactive glass or glass-ceramic,
characterised in that the inorganic component comprises at least
one metal oxide having an anti-bacterial activity, wherein said
glass or glass-ceramic is adapted to release ions of said metal in
contact with physiological fluids and wherein said antibacterial
ion is incorporated in the glass or glass-ceramic component,
additional phases other than glass or glass-ceramic including said
ion being absent.
18. A bone cement according to claim 17, comprising: from 10% to
80% by wt. of the glass or glass-ceramic component and from 20% to
90% by wt. of acrylic polymeric component, referred to the total
weight of said components.
19. A bone cement according to claim 17, wherein the glass or
glass-ceramic component comprises: SiO.sub.2: from 40% to 60% by
moles; CaO: from 15% to 45% by moles; Na.sub.2O: from 5% to 25% by
moles; and at least one oxide selected from silver oxides, zinc
oxide and copper oxide and mixtures thereof.
20. A bone cement according to claim 19, comprising one or more of
the following oxides: Ag.sub.2O: from 0.1% to 10% by moles,
preferably from 0.1% to 1% by moles; ZnO: from 0.1% to 20% by
moles, preferably from 0.1% to 10% moles; CuO: from 0.1% to 10% by
moles, preferably from 0.1% to 1% by moles; or mixtures of said
oxides, the amount of anti-bacterial metal oxides being not higher
than 20% by moles.
21. A bone cement according to claim 19, further comprising one or
more of the following compounds or mixtures thereof:
P.sub.2O.sub.5: from 0% to 10% by moles, preferably from 1% to 5%;
K.sub.2O: 0-10% by moles, preferably from 1% to 10%; MgO: 0-10% by
moles, preferably from 1% to 8%; Al.sub.2O.sub.3: 0-3% by moles,
preferably from 1% to 3%; B.sub.2O.sub.3: 0-3% by moles, preferably
from 1% to 3%; CaF.sub.2: 0-10% by moles, preferably from 1% to
9%.
22. A bone cement according to claim 17, wherein the polymeric
component comprises polymethylmethacrylate and/or
methylmethacrylate and methylacrylate copolymers or a polymer of
bisphenol-alpha-glycidylmethacrylate.
23. A composition for the production of a bone cement comprising: a
powder phase including an acrylic polymer component and a glass or
glassceramic component, which encloses an antibacterial metal ion,
according to claim 17 and optionally including a polymerisation
initiator and/or a radio-opacifying agent; and, a liquid phase
including an acrylic monomer and optionally a polymerisation
accelerator and/or inhibitor, and wherein the antibacterial metal
ion is only enclosed within the glass or glass-ceramic component,
any additional phase including said ion being absent.
24. A composition according to claim 23, wherein said powder phase
comprises: from 10% to 80% by wt. of glass or glass-ceramic
component; and from 20% to 90% by wt. of acrylic polymeric
component, referred to the total weight of said components.
25. A composition according to claim 24, wherein said glass or
glass-ceramic component comprises from 10% to 50% by wt. referred
to the total weight of said powder phase.
26. A bone cement according to claim 17, or a composition for the
manufacture of a bone cement according to claim 23, wherein said
bioactive glass or glass-ceramic component is obtained by an ion
exchange process in an aqueous solution containing antibacterial
metal ions, applied to a glass or glass-ceramic component powder
under pH conditions kept between 5 and 8.
27. A bone cement or a composition for the manufacture of a bone
cement, according to claim 26, wherein said glass or glass-ceramic
component exhibits an oxide composition such that when kept in
water, the release of chemical species from such a component is not
capable of bringing the pH to values higher than 8, under balance
conditions or for periods of less than 240 minutes.
28. A method for the manufacture of a bone cement according to
claim 17, comprising mixing at least one acrylic polymer component
and one powdered bioactive glass or glassceramic component
enclosing an antibacterial metal, characterised in that said glass
or glass-ceramic component is obtained by an ion exchange process
in an aqueous solution including one or more ions of an
antibacterial material, applied to a powder of said component,
under pH conditions kept between 5 and 8.
29. The method according to claim 28, wherein said glass or
glass-ceramic component exhibits a metal oxide composition such
that when kept in water, the release of chemical species from said
component is not capable of bringing the pH to values higher than
8, under balance conditions for periods of less than 240
minutes.
30. A method for fixation of orthopaedic prostheses comprising
applying to said prostheses a bone cement or a composition for the
manufacture of a bone cement according to claim 17.
31. A method for spinal surgery comprising applying a bone cement
according to claim 17, as a reinforcement cementing material.
Description
[0001] The present invention relates to acrylic polymer-based bone
cements capable of promoting osteointegration and simultaneously
preventing the onset of post-operative infections.
[0002] In the clinical practice, cemented fixation of orthopaedic
prostheses (hip, knee) implies the application of acrylic cements,
typically comprising in situ-polymerised polymethylmethacrylates
(PMMA).
[0003] PMMA cements are typically prepared from two components: a
liquid and a powder. The liquid includes methylmethacrylate (MMA)
monomers, an accelerator and/or inhibitor. The powder includes PMMA
microspheres, a polymerisation initiator and/or radio-opacifying
agent. These cements promote both the short-term and long-term
prosthesis stability, through a mechanical anchorage, yet they do
not become completely integrated with the bone tissue and exhibit
poor mechanical properties. The PMMA-based cement is also used for
making temporary prosthetic devices in case of revision.
[0004] A further use for this material is in spinal surgery in case
of vertebral fractures, wherein PMMA is injected into the fractured
vertebra for the consolidation thereof.
[0005] A significant problem in implant surgery is the possible
development of infections. Indeed, the temporary prosthetic devices
are often used during the infection treatment step by systemic or
localised antibiotic administration.
[0006] In recent years, several expedients have been established in
order to prevent the onset of periprosthetic infections; however,
even though the infection rate has decreased, the problem is not
completely solved. The possibility of introducing antibiotics
directly into the bone cement used for fixing the prosthesis, so as
to prevent the settlement of germs at the bone
tissue-cement-prosthesis interface, has been known since the '70s.
Since then, many investigations have been carried out to prove the
effectiveness of such a method, by using different antibiotics and
different bone cements.
[0007] Moreover, which way is the best way for introducing
antibiotics into the cement is presently under discussion; in fact,
the drug powder may be added manually during surgery to the polymer
powder, or the blend may be accomplished directly during
manufacture with industrial techniques.
[0008] In particular, the use of cements commercially-added with
antibodies developed mainly in European countries; in contrast, in
the United States it is preferred to introduce the required
antibiotic manually during surgery.
[0009] In spite of the great numbers of data present in literature,
very few studies actually compare commercially produced
antibody-added cements and cements added in situ with antibodies.
Even nowadays there is not a sufficient amount of extensive data
that prove the effectiveness of cements added with antibiotics.
[0010] Also bio-active bone cements containing PMMA, a bio-active
glass prepared from SiO.sub.2--CaO--P.sub.2O.sub.5 and antibiotics,
are known. Bio-active glasses described by L. L. Hench in
Bioceramics, J. Am. Ceram. Soc. 81 [7] (1998), 1705-1728 are
characterised by the fact that they are able to induce an actual
chemical bond with bone tissue, thanks to their ability of
interacting with biological fluids, thereby forming a
hydroxyapatite layer on the surface thereof.
[0011] Even though on one hand the use thereof can improve the
osteointegration characteristics, the problem remains of conferring
adequate and long-lasting antibacterial properties to the bone
cement.
[0012] In these cements, the antibody active principle normally is
mixed with the polymer phase and constitutes a third phase in the
cement composition.
[0013] Furthermore, the use of PMMA bone cements containing
antibacterial metal salts has been proposed; WO82/01990 describes a
bone cement for cementing prostheses, which contains
polymethylmethacrylate, a load of glass fibre or quartz particles
and a material designed to release silver ions in the form of a
colloidal silver salt. In this case, too, we are dealing with a
three-phase composition, in which it is difficult to regulate a
sustained release of the antibacterial metal ions. Moreover, the
glass phase is not bioactive.
[0014] One object of the present invention is to provide a novel
bone cement composition, particularly for use in the fixation of
orthopaedic prostheses, in spinal surgery or in the production of
temporary prostheses, made of acrylic polymers, which at the same
time is suitable to promote binding to the tissue with which it
comes into contact, and thus integration of the prosthetic device,
and suitable to effect a sustained antibacterial action.
[0015] For such a purpose, object of the invention is a bone cement
having the characteristics defined in the claims that follow.
[0016] In the bone cement object of the invention, the acrylic
polymer typically is polymethylmethacrylate (PMMA), but it may also
be made of a methylmethacrylate and methylacrylate copolimer, or by
a bisphenol-a-glycidylmethacrylate (bis-GMA) polymer or mixtures
thereof.
[0017] The glass/glass-ceramic component is introduced in the form
of a powder into the polymer component of the bone cement. The
mixture thus obtained is subsequently polymerised in situ by
stirring with the liquid monomer and the activator. Typically,
according to the conventional technique, the polymer component and
glass/glass-ceramic component mixture preferably contains a
powdered X ray opacifier, for example zirconium dioxide and/or
barium sulphate.
[0018] The liquid fraction contains the monomer, typically
methylmethacrylate, in which a radical activator is dissolved such
as for example N-N-dimethyl-p-toluidine. It is however understood
that the invention is not restricted to the selection of specific
initiators and/or radical activators.
[0019] The percentage of the glass/glass-ceramic component in the
polymerised bone cement generally is lower than 80% by weight,
referred to the total weight of the bone cement, and preferably is
lower than 50% by weight, so as to allow for an excellent
homogenisation with the acrylic polymer component. Percentages of
the glass/glass-ceramic component from 10% to 50% by weight are
preferred.
[0020] The granulometry of the glass powders, referred to as the
largest granule size, typically is lower than 80 .mu.m and
preferably lower than 20 .mu.m.
[0021] The bioactive glass/glass-ceramic component contains at
least the following oxides: SiO.sub.2, CaO, Na.sub.2O, as well as
at least one silver, zinc and/or copper oxide or mixtures thereof.
Preferably, the glass/glass-ceramic component comprises: [0022]
SiO.sub.2: 40-60% by moles; [0023] CaO: 15-45% by moles; [0024]
Na.sub.2O: 5-25% by moles; [0025] Ag.sub.2O: 0.1-10% by moles,
preferably 0.1-1% by moles; and/or [0026] ZnO: 0.1-20% by moles,
preferably 0.1-10% by moles; and/or [0027] CuO: 0.1-10% by moles;
the total amount of antibacterial metal oxides preferably being not
higher than 20% molar.
[0028] Further oxides may be added, such as P.sub.2O.sub.5,
K.sub.2O, MgO, Al.sub.2O.sub.3 e B.sub.2O.sub.3, individually or as
mixtures of two or more of the mentioned oxides. By way of example,
each of said oxides may be used in the glass composition in
accordance with the following molar concentrations: [0029]
P.sub.2O.sub.5: 0-10% by moles, preferably 1-5% by moles; [0030]
K.sub.2O: 0-10% by moles, preferably 1-10%; [0031] MgO: 0-10% by
moles, preferably 1-8%; [0032] Al.sub.2O.sub.3: 0-3% by moles,
preferably 1-3%; [0033] B.sub.2O.sub.3: 0-3% by moles, preferably
1-3%; [0034] CaF.sub.2: 0-10% by moles, preferably 1-9%;
[0035] The glass/glass-ceramic component can be obtained by fusion
of precursors of the above-mentioned oxides, typically carbonates.
Alternatively, the glass/glass-ceramic component can be obtained by
the sol-gel process.
[0036] The per se known sol-gel synthesis method is performed by
stirring the metal alkoxides in solution, followed by hydrolysis,
gelatinization and baking
[0037] The antibacterial element can be inserted into the
composition in the form of an oxide during synthesis of the glass
(or glass-ceramic) or preferably in an ion form, after synthesis,
through ion exchange processes from solutions, for instance
according to the method described in EP 1 819 372.
[0038] The ion exchange technique allows even high amounts of
silver to be introduced into the glasses and glass-ceramics of
suitable composition, which is difficult to achieve by the fusion
and casting technique. Usually, the bio-glasses are synthesised by
using refractory pots, therefore a high silver content may cause
interactions between the silver and the pot, with formation of
unwanted phases, and consequent non-uniform silver content in the
different castings. Furthermore, the fusion and casting technique
does not allow for an excellent silver dispersion and
homogenisation within the material, with frequent formation of
metal clusters (FIG. 1).
[0039] EP 1 819 372 describes the bulk application of the ion
exchange method to glass and/or glass-ceramic materials or on metal
coatings. For application on powders, the process parameters need
to be suitably modified and controlled; in fact, the same
conditions applied for instance to bulks and powders give decidedly
different results.
[0040] Particularly the ion exchange technique on powders must be
carefully examined for each specific glass/glass-ceramic
composition employed, even considering parameters, such as for
example the pH value of the exchange solutions, which generally do
not have effect during the process performed on bulks, coatings and
scaffolds.
[0041] The high specific surface of powders makes them more
reactive towards the surrounding environment and particularly
during the ion exchange process in solution. For instance, glass
powders (Example 1 composition), subjected to ion exchange under
the same conditions of bulks and coatings with an identical
composition, show precipitation of silver carbonate as a result of
reaction between Ag+ ions and CO.sub.2 or the carbonates in the
reaction environment (FIG. 2.a, FIG. 3). The presence of silver
carbonate precipitates on the bioactive glass powders, instead of
ions diffused therein, does not ensure a gradual and sustained
release of silver ions and establishes an uncontrollable phenomenon
of a third phase formation. Powders with the same glass composition
containing Ag or the other antibacterial ions previously mentioned,
without precipitation of second phases, can be obtained only by
carefully selecting the process parameters. (FIG. 2.b).
[0042] As previously anticipated, in order to obtain powders with
an adequate dosage of silver ions without precipitation of other
phases, not only the normal exchange parameters (time, temperature
and concentration of the exchange solution) need to be varied and
controlled, but also further parameters such as for example the pH
of the exchange solutions.
[0043] In fact, precipitation of carbonates is favoured at highly
basic pHs; instead, the maintenance of a pH between 5 and 8,
preferably comprised between 7 (neutral) and 7.6, allows to favour
maintenance of the antibacterial ions (e.g. silver) in solution,
and thus a suitable diffusion thereof within the glass particles.
Such a pH control could be carried out by adding a buffer to the
exchange solutions; this solution however is not applicable to this
specific case since it induces formation of other silver salt
precipitates (chlorides, phosphates . . . ). In the application
according to the invention it is preferable to use a glassy
composition, the ion release of which does not make the solution
highly basic (FIG. 4).
[0044] Thus, a relevant and preferred feature of the bone cements
object of the invention is that the antibacterial agent is only
incorporated in the glass or glass-ceramic material and additional
phases other than glass or glass-ceramic made of or enclosing the
antibacterial agent are absent, such as for example inter-metal
phases or metal clusters or precipitates including the
antibacterial agent.
[0045] Therefore, the bone cement composition according to the
invention is essentially a monophasic composition with regard to
the phases that include the antibacterial agent.
[0046] Such a feature allows to obtain a controlled release of the
antibacterial ions when the bone cement is applied in situ in
contact with physiological fluids.
[0047] To that end, it is thus preferable to prepare the bone
cement by using glass or glass-ceramic material powder subjected to
ion exchange in an aqueous solution containing antibacterial metal
ions; the ion exchange process is carried out at temperatures below
100.degree. C., preferably from 37 to 100.degree. C., for periods
of from 15 to 240 minutes, at a pH comprised between 5 and 8, by
using a powdered glass or glass-ceramic material that includes
metal ions (e.g. alkaline or alkaline earth materials) liable to
exchange with the antibacterial ions (particularly silver).
[0048] In particular, a bioactive powdered glass or glass-ceramic
material is used, the oxide composition of which is such that, when
the material is kept in water, the release of chemical species from
such a material is not capable of bringing the pH to values higher
than 8, under balance conditions or for periods of up to 240
minutes.
[0049] Examples of compositions suitable for maintaining a neutral
pH:
TABLE-US-00001 % wt % mol % wt % mol SiO.sub.2 49 49.81 SiO.sub.2
46.53 48 Na.sub.2O 24 23.61 Na.sub.2O 18.03 18 CaO 22 23.96 CaO
27.14 30 P.sub.2O.sub.5 3.2 1.37 P.sub.2O.sub.5 6.88 3
B.sub.2O.sub.3 0.6 0.53 B.sub.2O.sub.3 0.48 0.43 Al.sub.2O.sub.3
1.2 0.72 Al.sub.2O.sub.3 0.94 0.57 TOT 100 100.00 TOT 100.00
100
[0050] Further advantages and features of the bone cement according
to the invention will be apparent from the following examples.
[0051] In the appended drawings:
[0052] FIG. 1 illustrates a glass frit containing 1% wt of Ag
obtained by fusion and casting. The yellow colouring is likely due
to the presence of nano-clusters.
[0053] FIG. 2 illustrates the X ray analysis of glass powders with
a composition according to Example 1, exchanged under the same
conditions as bulks and coatings (a) and under optimised ion
exchange conditions (b).
[0054] FIG. 3 reports SEM and EDS analyses of precipitates
containing silver on powders exchanged under the same conditions as
bulks and coatings.
[0055] FIG. 4 illustrates an XRD analysis of glass powders that
bring the pH of the exchange solutions at highly basic values (a)
and of glassy powders (prepared according to Example 3) which
instead favour the maintenance of a neutral or slightly basic pH
(b) exchanged under the same conditions.
[0056] FIG. 5 illustrates SEM micrographs and an EDS analysis of a
composite cement prepared according to Example 5b;
[0057] FIG. 6 illustrates the inhibition halo of composite cements
prepared according to Example 4;
[0058] FIG. 7 illustrates the inhibition halo of composite cements
prepared according to Example 5b;
[0059] FIG. 8 is a diagram that illustrates the release trend of
the silver ion from composite cements prepared according to Example
4.
[0060] FIG. 9 illustrates the inhibition halo of low-(a) and
high-(b) viscosity composite cements prepared according to Example
6.
EXAMPLE 1
Preparation of the Bioactive Glass Component
[0061] A bioactive glass having the following composition was
prepared: [0062] SiO.sub.2: 57% by moles [0063] CaO: 34% by moles
[0064] Na.sub.2O: 6% by moles [0065] Al.sub.2O.sub.3: 3% by
moles
[0066] The glass was prepared by using SiO.sub.2, CaCO.sub.3,
Na.sub.2CO.sub.3, Al.sub.2O.sub.3 as the oxide precursors.
[0067] The fusion process was performed at a temperature of about
1400.degree. C.-1550.degree. C. and the molten was poured out into
water to obtain powders.
[0068] The powder thus obtained was milled and sieved to a size
smaller than 20 .mu.m. The powders were added with silver ions by
replacement of sodium ions through ion exchange in aqueous silver
nitrate solutions, thereby obtaining a final glass composition of:
[0069] SiO.sub.2: 57% by moles [0070] CaO: 34% by moles [0071]
Na.sub.2O: 5.9% by moles [0072] Al.sub.2O.sub.3: 3% by moles [0073]
Ag.sub.2O: 0.1% by moles
EXAMPLE 2
Preparation of the Bioactive Glass Component
[0074] The synthesis was carried out as in Example 1, by including
though directly the silver oxide in the form of Ag.sub.2CO.sub.3
within the precursors, thereby obtaining a glass having the
following molar composition: [0075] SiO.sub.2: 50% by moles [0076]
CaO: 24% by moles [0077] Na.sub.2O: 22.2% by moles [0078]
Al.sub.2O.sub.3: 0.7% by moles [0079] P.sub.2O.sub.5: 1.4% by moles
[0080] B.sub.2O.sub.3: 1.4% by moles [0081] Ag.sub.2O: 0.3% by
moles
EXAMPLE 3
Preparation of the Bioactive Glass Component
[0082] A bioactive glass having the following composition was
prepared: [0083] SiO.sub.2: 48% by moles [0084] CaO: 30% by moles
[0085] Na.sub.2O: 18% by moles [0086] P.sub.2O.sub.5: 3% by moles
[0087] Al.sub.2O.sub.3: 0.57% by moles [0088] B.sub.2O.sub.3: 0.1%
by moles
[0089] The glass was prepared as in Example 1 and silver ions were
added by replacement of sodium ions through ion exchange in aqueous
silver nitrate solutions, as in Example 1.
EXAMPLE 4
Preparation of the Cement
[0090] The powder obtained as in Example 1 was mixed with a
polymeric polymethylmethacrylate component according to the
following ratios: [0091] PMMA: 50% by weight [0092] glass
components: 50% by weight
EXAMPLE 5
Preparation of the Cement
[0093] The powder obtained as in Example 2 was mixed with a
polymeric polymethylmethacrylate component according to the
following ratios:
[0094] EXAMPLE 5a [0095] PMMA: 70% by weight [0096] glass
components: 30% by weight
EXAMPLE 5b
[0096] [0097] PMMA: 50% by weight [0098] glass components: 50% by
weight
[0099] The tests performed demonstrated that the bioactive
glasses/glass-ceramics, even when included in the polymeric acrylic
composition, are capable of promoting the formation of a
hydroxyapatite layer on their surface subsequent to reaction with
mock physiological fluids.
EXAMPLE 6
Preparation of the Cement
[0100] The powder obtained as in Example 3 was mixed with a
polymeric polymethylmethacrylate component according to the
following ratios: [0101] PMMA: 70% by weight [0102] glass
components: 30% by weight A micrograph of the surface of a
composite cement prepared according to Example 5b is reported by
way of example, where formation of hydroxyapatite is observed after
immersion in a mock physiological solution for 28 days (FIG.
5).
[0103] The presence of a bioactive phase that becomes exposed on
the cement surface causes this structure to promote the binding in
vivo to the tissue with which it comes into contact, and thus
integration of the prosthesis thus cemented. The presence of the
glass/glass-ceramic component also has the advantage of decreasing
the local temperature rise due to the exothermic character of the
polymerisation reaction, with undisputed advantages for the bone
directly in contact with the cement.
[0104] Moreover, adding the second glass/glass-ceramic phase does
not alter the material's processing and hardening properties
[0105] In addition, the presence of the inorganic phase in the bone
cement contributes to enhancing the cement's mechanical
properties.
[0106] By suitably varying the glass composition and the parameters
for the introduction of the antibacterial oxide, it is possible to
modulate the bioactivity degree of the cement, the release kinetics
of the metal ions and the mechanical properties of the composite
material, depending on the particular application requirements.
[0107] The antibacterial tests on the bone cement were carried out
by using each of the cement types mentioned in Examples 4, 5,
6.
[0108] The antibacterial effect of the composite cements was
assessed by the inhibition halo test according to the NCCLS
(National Committee for Clinical Laboratory) standards. Such a
trial contemplates preparing a solution of known bacterial
concentration and diffusing an aliquot of such a solution onto
Mueller Hinton plates, which allow the bacteria to grow rapidly.
The samples are placed on the plates containing the bacteria and
incubated at 35.degree. C. for 24 hours. At the end of the
incubation the area where the bacteria did not grow is examined and
measured.
[0109] The antibacterial tests were carried out by using a standard
Staphylococcus Aureus strain, one of the bacterial strains most
involved in the development of infections.
[0110] FIG. 6 shows a comparison between a bone cement manufactured
according to Example 4 and a cement loaded with powders from the
same bioactive glass without silver oxide.
[0111] FIG. 7 illustrates the antibacterial effect obtained with
the cements described in Example 5b. FIG. 8 shows the antimicrobial
capacity of cements described in Example 6 containing the glass
dosed with silver through ion exchange with optimised parameters
(Example 3).
[0112] The test results further demonstrate that the bone cement
according to the invention allows to obtain a sustained release of
antibacterial metal ions with an activity that lasts for periods of
from about 7 days to more than a month and therefore results
advantageous compared to the restricted antibacterial activity
periods of bone cements loaded with antibiotics.
* * * * *